Question 1

Chronic respiratory tract infections, including acute bacterial exacerbations of chronic bronchitis (ABECB) and acute exacerbations of COPD (AECOPD) are a common and pervasive problem, associated with significant morbidity. Could you comment on the rationale for using antimicrobials to treat such patients?

COPD is one of the most common respiratory conditions of adults in the developed world. An estimated 14 million people in the United States are currently diagnosed with COPD (1). Patients with COPD are prone to frequent exacerbations, a significant cause of morbidity (i.e., physician visits, emergency department visits and hospitalizations) and mortality. COPD is the fourth leading cause of death in the world, with annual mortality predicted to rise from 2.25 million deaths in 1990 to an estimated 4.5 million deaths in 2020 (2). Respiratory failure, which may develop as a consequence of an acute exacerbation, is a major cause of death in patients with COPD.
There are a number of triggers of acute exacerbations including tracheobronchial infections or environmental exposures; acute exacerbations may also be precipitated by such clinical conditions as heart failure, extrapulmonary infection and pulmonary embolism. Among these, respiratory tract infections are the most common cause of acute exacerbations (1). From 40 to 60% of these infections are bacterial in origin, and Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae are the most commonly isolated organisms (3). In support of the causative role of bacteria in exacerbations of COPD, recent studies have demonstrated a significant association between an exacerbation and the isolation of new strains of bacterial pathogens (Table 1) (4).
Table 1. Relative risk of an exacerbation according to whether a new strain or bacterial pathogen was isolated

New strain	Frequency of exacerbation		p value	Relative risk (95% CI) a
	New strain	No new strain
	No. of exacerbations/total no. of visits (%)
Any strain	89/270 (33.0)	213/1,385 (15.4)	< 0.001	2.15 (1.83-2.53)
Haemophilus influenzae	38/145 (26.2) b	257/1,503 (17.1)	< 0.001	1.69 (1.37-2.09)
Moraxella catarrhalis	41/84 (48.8)	261/1,571 (16.6)	< 0.001	2.96 (2.39-3.67)
Streptococcus pneumoniae	8/25 (32.0)	294/1,630 (18.0)	0.01	1.77 (1.14-2.75)
Pseudomonas aeruginosa	3/22 (13.6) c	297/1,631 (18.2)	0.38	0.61 (0.21-1.82)
a  The relative risk of an exacerbation was for the presence of a new strain in sputum, as compared with its absence. Relative risks were calculated with the use of generalized estimating equations. b  Seven visits were excluded because of simultaneous isolation of new strains of M. catarrhalis (six visits) and P. aeruginosa (one visit). c  Two visits were excluded because of simultaneous isolation of new strains of M. catarrhalis. Abbreviation: CI = confidence interval. Adapted from reference (4).